依那普利对自发性高血压大鼠心脏局部Ang Ⅱ、ACE和Chymase活性的影响

目的研究自发性高血压大鼠(SHR)心脏局部AngⅡ、ACE和Chymase活性及ACEI依那普利对其影响,探讨ACE和Chymase对SHR心脏局部AngⅡ形成的作用.方法12周龄SHR 40只,随机分为两组,一组依那普利治疗30 mg/(kg·d),另一组作为对照,同时设一同周龄的WKY作为正常对照,测量各组的AngⅡ浓度、ACE和Chymase活性.结果(1)SHR组AngⅡ浓度为(5.780±3.734)ng/(mg组织),显著高于WKY组(2.723±0.84)ng/(mg组织)(P＜0.05);而依那普利治疗SHR-d组AngⅡ浓度为(2.757±2.717)ng/(mg组织),与WKY组相比无统计学意义(P＞0.05).(2)SHR、SHR-d、WKY 3组ACE活性分别为(0.60±0.13)U/(mL·mg组织),(0.47±0.12)U/(mL·mg组织),(0.45±0.19)U/(mL·mg组织),SHR组与SHR-d、WKY两组比较均差异有显著性(P＜0.05),SHR-d组与WKY组比较差异无显著性(P＞0.05).(3)Chymase活性测定,SHR组为(28.65±7.51)nmol/(min·mg组织),SHR-d组为(27.69±8.61)nmol/(min·mg组织),WKY组(27.68±8.16)nmol/(min·mg组织),3组两两比较均差异无显著性(P＞0.05).结论应用ACEI能有效抑制SHR心脏局部AngⅡ生成,提示ACE在SHR心脏局部AngⅡ形成中其重要作用.     

缬沙坦对自发性高血压大鼠心脏、胸主动脉血管紧张素转换酶2表达的影响

目的探讨血管紧张素转化酶2(ACE2)在自发性高血压大鼠(SHR)心脏及胸主动脉中的表达以及缬沙坦对其的影响。方法 24只SHR随机分为SHR组(n=12)、缬沙坦组(n=12),12只血压正常的Wistar大鼠作为正常对照组,缬沙坦组每只大鼠给予缬沙坦30mg.kg-1.d-1灌胃,SHR组及正常对照组给予等量生理盐水灌胃。10周后,应用光镜观察心肌的病理变化,测定主动脉中膜厚度与血管腔内径之比。免疫组化法检测心肌、主动脉中ACE2的表达。结果与正常对照组比较,SHR组心肌、主动脉中ACE2表达显著降低(P<0.05);与SHR组比较,缬沙坦组ACE2表达显著增高(P<0.05),缬沙坦组血压、心脏重量指数较SHR组均明显下降(P<0.05)。结论自发性高血压大鼠心肌、主动脉中ACE2表达降低,缬沙坦能够上调SHR心肌、主动脉中ACE2的表达,该作用可能为血管紧张素Ⅱ1型受体拮抗剂抑制高血压病所导致的心血管重构的新机制。     

坎地沙坦对自发性高血压大鼠骨骼肌核转录因子-2表达和胰岛素敏感性的影响

目的：研究坎地沙坦对自发性高血压大鼠骨骼肌核转录因子-2（Nrf2）表达和胰岛素敏感性的影响。方法30只自发性高血压大鼠随机分为对照组（C 组）、模型组（M组）、坎地沙坦低剂量组（Can1组）、坎地沙坦高剂量组（Can2组）,10只 WKY 大鼠作为对照组,均给予果糖喂养,Can1组及 Can2组分别给予坎地沙坦（0．4 mg／kg、0．8 mg／kg）灌胃干预。实验第8周末,检测各组大鼠胰岛素抵抗指数（HOMA-IR）、血管紧张素Ⅱ（AngⅡ）、活性氧（ROS）以及 Nrf2的表达水平。结果与 C 组相比,M组 HOMA-IR 水平及 ROS 表达显著升高,而 Nrf2表达降低,差异有统计学意义（P ＜0．05、P ＜0．01）;与 M组相比,Can2组的 ROS 生成减少,HOMA-IR 下降,差异有统计学意义（P ＜0．05、P ＜0．01）;Can1及 Can2组的 Nrf2表达均较 M组显著增加,差异有统计学意义（P ＜0．05、P ＜0．01）。结论坎地沙坦可以通过拮抗 AngⅡ减轻 AngⅡ诱导的骨骼肌胰岛素抵抗和氧化应激。     

血管紧张素Ⅱ对自发性高血压大鼠外周血单个核细胞NADPH氧化酶2表达的影响

目的:探讨血管紧张素Ⅱ(AngⅡ)对自发性高血压大鼠(SHR)外周血单个核细胞NADPH氧化酶2(NOX2)表达的影响.方法:分离SHR外周血单个核细胞并进行培养,将细胞随机分为4组(n=6):空白对照组、Ang Ⅱ(10-8 mol/L)组、Ang Ⅱ(10-7 mol/L)组和Ang Ⅱ(10-6 mol/L)组.RT-PCR检测NOX2 mRNA的表达,Western blot检测NOX2蛋白的表达.结果:与空白对照组相比,Ang Ⅱ(10-8、10-7mol/L)组NOX2 mRNA的表达差异无显著性(P>0.05),而NOX2蛋白的表达升高(P<0.01),Ang Ⅱ(10-6mol/L)组NOX2mRNA及蛋白的表达均明显升高(P<0.01).结论:Ang Ⅱ可以促进高血压外周血单个核细胞NOX2的激活.     

替米沙坦对自发性高血压大鼠颈动脉重构的影响

目的:观察替米沙坦对自发性高血压大鼠(SHR)颈动脉重构的影响。方法:将 30只12周龄的SHR大鼠随机分为高血压组(SHR)、替米沙坦高剂量组(TelH)、替米沙坦低剂量组(TelL),另设同性别、周龄的10只WKY 大鼠为对照组。实验开始及每2周测鼠尾收缩压(SBP)。18周后取颈动脉,颈动脉的切片行苦味酸-天狼星红、弹力纤维和胶原纤维的双重染色法染色,利用计算机辅助成像系统测算颈动脉中膜厚度(MT)、腔径(LD)、血管中膜厚/腔径(MT/LD)、中膜横截面积(MCSA)及中膜胶原面积百分比、弹性纤维面积百分比、弹性纤维面积与胶原面积比值。结果:(1)2周后TelH组的SBP显著低于SHR组(P<0.01),而TelL组的SBP与 SHR组差异无显著性(P>0.05);(2)TelH组的MT、MT/LD、MCSA、中膜胶原面积百分比较SHR组均显著下降(P< 0.01),TelH组的中膜弹性纤维面积百分比、弹性纤维面积与胶原面积比值较SHR组均显著增高(P<0.01);TelL组的MT、中膜胶原面积百分比均显著下降(P<0.05),中膜弹性纤维面积与胶原面积比值显著增高(P<0.01)。结论:替米沙坦能减轻SHR...     

血清中血管紧张素转换酶测定的临床应用

血管紧张素转换酶（ACE）是一种二肽羧肽酶，主要分布在肺泡毛细血管内皮表面，其主要作用是水解血管紧张素Ⅰ（AngⅠ）转化成血管紧张素Ⅱ（AngⅡ）。现对其结构、测定方法、临床应用等方面作一介绍。     

手术型高血压大鼠模型肾脏血管紧张素转换酶、血管紧张素转换酶2表达变化的研究

目的建立手术型高血压大鼠模型,观察肾脏血管紧张素转换酶(ACE)、ACE2mRNA及蛋白在各组中的表达变化情况,进一步探讨高血压发病的变化因素和相关治疗机制。方法 28只SD大鼠,随机分为对照组(n=7)、高血压组(n=7)、依那普利组(n=7,10mg·kg-1·d-1)及氯沙坦组(n=7,15mg·kg-1·d-1),其中除对照组外的21只大鼠通过不完全结扎肾动脉(保留0.7mm的动脉口径)制成高血压模型。使用RT-PCR的方法检测肾脏ACE及ACE2mRNA表达变化情况,使用免疫组织化学的方法检测肾脏ACE及ACE2蛋白表达变化情况。结果术后大鼠血压升高,造模成功;各组之间ACE、ACE2mRNA及蛋白表达程度不同;高血压组ACE表达强于其他各组(IOD=0.592,P<0.05),氯沙坦组ACE2表达强于其他各组(IOD=0.760,P<0.05);高血压组ACE与ACE2表达比例明显失衡(P<0.05),对照组、依那普利组及氯沙坦组ACE与ACE2表达比例较为平衡(P>0.05)。结论结扎肾动脉造模成功,ACE、ACE2表达的失衡是高血压发病的重要影响因素,调整两者表达的平衡是重要的治疗机制。     

IgA肾病与局部肾素-血管紧张素系统

IgA肾病占原发性肾小球疾病的26%～34%.被确诊IgA肾病的患者,20年内进展至终末期肾病(ESRD)者占25%～30%.目前认为,系膜病理性IgA沉积与肾局部肾素-血管紧张素系统(RAS)的激活,在IgA肾病进展中起关键作用,而血管紧张素转换酶抑制剂(ACEI)与血管紧张素受体阻断剂(ARB)的使用有效阻断肾局部RAS,缓解IgA肾病肾损伤及纤维化的发生.     

血清中血管紧张素转换酶测定的临床应用

血管紧张素转换酶(ACE)是一种二肽羧肽酶,主要分布在肺泡毛细血管内皮表面,其主要作用是水解血管紧张素Ⅰ(AngⅠ)转化成血管紧张素Ⅱ(AngⅡ)。现对其结构、测定方法、临床应用等方面作一介绍。     

厄贝沙坦和咪达普利对早期雄性自发性高血压大鼠凝血和纤溶系统的影响

背景 目前对于高血压凝血和纤溶系统的改变存在着争议 , 而凝血和纤溶系统在高血压血栓栓塞性和 /或出血性并发症的进程中具有关键性作用,因此,检测高血压患者的凝血和纤溶状态 ,并以此为依据合理选用能改善其凝血和纤溶状态的抗高血压药以及据此提出合理的康复介入方案,具有不容忽视的临床价值. 设计 随机对照的实验研究. 目的 探讨厄贝沙坦和咪达普利在降压的同时 , 对早期雄性自发性高血压大鼠( spontaneously hypertensive rats, SHR)血浆凝血酶原时间、纤维蛋白原含量、组织型纤溶酶原激活物活性( tissue-type plasminogen activator activity, t-PAA)、纤溶酶原激活物抑制剂活性( plasminogen activator inhibitor activity, PAIA)和α 2 纤溶酶抑制物活性(α 2 plasmin inhibitor activity,α 2-PIA)的影响. 地点、材料和干预本实验在武汉大学医院检验中心进行. 15周龄雄性 SHR 30只按随机数字表法分为 3组,咪达普利组给予含咪达普利的水 3 mg/( kg· d);厄贝沙坦组给含厄贝沙坦的水 50 mg/( kg· d); SHR对照组和同龄雄性 Wistar Kyoto( WKY)大鼠 (正常血压对照组 )10只以等量蒸馏水代替;采用一期法检测血浆凝血酶原时间,采用凝血酶法检测血浆纤维蛋白原含量,采用发色底物法检测血浆 t-PAA, PAIA和α 2-PIA. 主要观察指标厄贝沙坦和咪达普利对 SHR凝血、纤溶系统的作用结果并与正常血压对照组( WKY大鼠)进行比较. 结果 与 WKY组比较 SHR对照组血浆纤维蛋白原含量显著增高( P< 0.01), t-PAA显著增高( P< 0.05) ,α 2-PIA显著降低( P< 0.01) , 而凝血酶原时间和 PAIA无明显变化.与 SHR对照组比较咪达普利组和厄贝沙坦组经过 3个月治疗血压明显降低( P< 0.01),纤维蛋白原含量显著降低( P< 0.01),α 2-PIA显著增高( P< 0.01). 结论早期雄性 SHR血管内凝血与纤溶并存,厄贝沙坦和咪达普利对早期雄性 SHR的干预能逆转 SHR慢性隐性 DIC所致的血栓前状态和动脉粥样硬化,改善其已受损的凝血和纤溶系统,从而降低出血性和 /或血栓栓塞性并发症的危险性.     

依那普利对百草枯中毒大鼠肺组织ACE表达的影响

目的：观察依那普利对百草枯（PQ）中毒大鼠肺组织病理改变、血管紧张素转化酶（ACE）表达的影响。方法一次性PQ 60 mg/kg灌胃建立大鼠百草枯中毒肺纤维化模型,干预组染毒后予依那普利10 mg/（kg·d）灌胃。于染毒后3 d、7 d、14 d取肺组织行HE染色和Masson染色,观察大鼠肺泡炎、肺纤维化程度;Quantitative Real-Time PCR检测ACE mRNA表达。结果干预组在染毒后3d、7d肺泡炎症减轻;染毒7d、14d后,纤维化程度积分低于模型组。模型组染毒后各时间点大鼠肺组织ACE mRNA表达逐步上调,持续至14 d。干预组各时间点ACE mRNA低于模型组。结论依那普利可能通过降低局部ACE表达,从而减轻百草枯中毒所致肺纤维化形成。     

自发性高血压大鼠肠系膜动脉重塑及厄贝沙坦和咪哒普利的影响

目的探讨自发性高血压大鼠(SHR)肠系膜动脉重塑以及转化生长因子-β1和c-Jun的表达和厄贝沙坦、咪哒普利的影响。方法选用13周龄的SHR30只,,随机分为3组,分别设为SHR组、厄贝沙坦组(饮水中加入厄贝沙坦)、咪哒普利组(饮水中加入咪哒普利);另选同源同系WKY大鼠10只,作为正常对照组(WKY组)。实验期14周。实验前,实验第1,2,4,6,8,12,14周测尾动脉收缩压一次。实验终止后处死动物,用光镜、电镜观察肠系膜动脉二级分支的形态学,用反转录-聚合酶链反应检测肠系膜动脉TGF-β1和c-JunmRNA水平。结果SHR组血压、肠系膜动脉TGF-β1和c-Jun的表达明显增高;咪哒普利组、厄贝沙坦组血压控制良好,肠系膜动脉重塑的各项指标改善,在这些指标上二者无显著性差异。肠系膜动脉结构改变尤其是纤维化均减轻,咪哒普利组减轻更明显;肠系膜动脉TGF-β1和c-JunmRNA的表达降低;咪哒普利组c-Jun和TGF-β1的表达比厄贝沙坦组低,分别为(0.743±0.012)vs(0.789±0.013)及(0.803±0.005)vs(0.847±0.017)。结论SHR肠系膜动脉重塑明显而且TGF-β1和c-JunmRNA的表达明显增高;咪哒普利、厄贝沙坦不仅能良好地控制血压而且可以抑制自发性高血压大鼠肠系膜动脉TGF-β1和c-JunmRNA的表达;咪哒普利对TGF-β1和c-JunmRNA表达的抑制作用比厄贝沙     

ACE inhibitors. A safe option for hypertension and congestive heart failure

The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure has recently recommended angiotensin-converting enzyme (ACE) inhibitors, beta blockers, and diuretics as potential first-step agents for the pharmacologic treatment of hypertension. ACE inhibitors should be considered an important option in most patients because of their safety profile, absence of adverse metabolic effects, and positive cardiac and renal effects. If the response to an ACE inhibitor is inadequate, a diuretic or another agent can be added, and this combination should be effective and well tolerated in 85% to 90% of patients. ACE inhibitors can be used to treat congestive heart failure and to prevent the renal complications of hypertension and diabetes mellitus, significantly expanding their use in patients with these high-risk conditions. They also can be used concurrently with other antihypertensive agents, digitalis, cardiac glycosides, and lithium and are not contraindicated in most of the diseases commonly seen in hypertensive patients.     

Enalapril in chronic heart failure, a double-blind placebo-controlled study

The efficacy of enalapril, a new angiotensin-converting enzyme inhibitor, was investigated in a double-blind placebo-controlled study in 24 patients with chronic heart failure. The patients belonging to NYHA functional class II-IV and treated with digoxin and diuretics were randomized to enalapril (12 patients) or placebo (12 patients) treatment for a 12-week period. Assessments were carried out at baseline and at 4 and 12 weeks during the treatment period. Complete data could be obtained on 10 patients receiving enalapril and on 11 patients receiving placebo. NYHA functional class improved by at least one class in 6 of 10 patients in the enalapril group, but only in 1 of 11 patients in the placebo group (chi 2 = 6.54; p less than 0.05). Duration of bicycle ergometer exercise increased significantly in the enalapril group from 8.8 +/- 3.4 to 11.3 +/- 4.2 (4 weeks) and to 11.2 +/- 3.6 min (12 weeks; p less than 0.05 for both), whereas it remained unchanged in the placebo group. Left ventricular ejection fraction by radionuclide ventriculography in the enalapril group increased significantly (baseline: 33.5 +/- 19.9%, 4 weeks: 40.0 +/- 20.0% (p less than 0.001), 12 weeks: 39.6 +/- 20.1% (p less than 0.01], whereas in the placebo group it did not change significantly from the baseline of 48.8 +/- 16.7%. The results indicate that enalapril induces a sustained relief of symptoms and improves exercise capacity in patients with heart failure. This subjective improvement appears to be accompanied by an increase in ejection fraction.     

Trace elements during the development of hypertension in the spontaneously hypertensive rat

Total plasma concentrations of bromine, copper, rubidium, selenium and zinc were measured in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) of 5-20 weeks of age, using an X-ray fluorescence spectrometry technique. Although plasma levels of bromine, rubidium, selenium and zinc varied at different ages when comparing SHR and WKY, their general evolution was similar. Copper levels increased more in SHR than in WKY. These perturbations in trace element levels could perhaps participate in the establishment of hypertension in SHR, but could also be due to genetic differences between the strains, unrelated to the development of hypertension.     

依那普利联用氢氯噻嗪对高血压的疗效观察

目的研究依那普利与氢氯噻嗪联用在我国治疗高血压患者的疗效。方法氢氯噻嗪12.5mg,1次/d口服,依那普利从小剂量开始2.5mg,渐增至10mg,2次/d,共治疗4周。结果4周末患者平均收缩压和舒张压均较治疗前显著下降,平均由[（20.3±0.9）/（13.2±0.7）]kPa,下降到[（17.4±1.2）/（10.9±1.3）]kPa,（P〈0.01）。结论依那普利与氢氯噻嗪联用疗效高,副作用少。     

Renal permeability alteration precedes hypertension and involves bradykinin in the spontaneously hypertensive rat.

Vascular permeability disorders have been described in experimental models, as well as in human hypertension. We recently described the fact that vascular permeability to albumin is heterogeneous in the normal rat. In the present study, we examine the contents of Evans blue dye (EB) bound to albumin in selected organs of unanesthetized Wistar Kyoto (WKY) and in spontaneously hypertensive rats (SHR) at various stages of development of hypertension. EB was injected in the caudal vein of paired 4, 8, 12, and 16-wk-old WKY and SHR. Rats were killed 10 min after EB injection and extraction of the marker was measured in selected tissues. In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB. Renal contents of EB bound to albumin were higher in the SHR than in the WKY: 196 +/- 9, 202 +/- 10, 182 +/- 7, and 196 +/- 9, compared with 158 +/- 8, 155 +/- 7, 138 +/- 7, and 118 +/- 6 micrograms/g dry tissue, in the 4, 8, 12, and 16-wk-old rats, respectively. In the 4-wk-old SHR and WKY, blood pressure values were normal and comparable, yet the alteration in EB permeability was already present in the SHR. Both BKA failed to alter the renal EB extravasation in the WKY, but the B2-BKA restored the renal permeability to control levels in the SHR. We conclude that a selective defect in the renal vascular permeability to EB developed in the SHR. Since this finding precedes hypertension and is corrected by a selective B2-BKA, it is suggested that bradykinin is involved at an early stage of the disease in the SHR.     

运动对自发性高血压大鼠肾小球胶原含量早期变化的影响

目的:探讨运动对高血压大鼠肾小球胶原含量变化的影响。方法:自发性高血压大鼠随机分为实验组和对照组,10周后检测体重、血压,应用生物显微图像分析系统检测肾小球胶原含量的变化。结果:实验组与运动前相比血压降低了6.2%,对照组10周后血压升高了7.9%,实验组血压非常显著低于对照组(P<0.01);SHR实验组体重显著低于对照组体重(P<0.05);实验组肾小球胶原球密度显著低于对照组(P<0.01)。结论:自发性高血压大鼠早期已出现肾小球形态变化,细胞外基质增加显著,肾小球胶原累积可能是肾小球硬化的早期改变;长期规律适量的运动对自发性高血压大鼠体重、血压的升高及肾小球的增加有一定的缓解作用。